Dimethylcarbamoyl Chloride → 6-Acetylpyridine-2-carbonitrile

HRID 1735974Notes

Reaction equation

HRID 1735974 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][N+:5]=1[O-])(=[O:3])[CH3:2].[CH3:11][N:12](C)C(Cl)=O.C([Si](C)(C)C)#N.C([O-])([O-])=O.[K+].[K+]>C(Cl)Cl>[C:1]([C:4]1[CH:9]=[CH:8][CH:7]=[C:6]([C:11]#[N:12])[N:5]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 6598Dimethylcarbamoyl Chloride2×HCID 11430Potassium CarbonateHCID 82115Trimethylsilyl cyanide2×HCID 3379981-(1-oxidopyridin-6-yl)ethanone

Product 1

HCID 152188056-Acetylpyridine-2-carbonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a solution of 2-acetylpyridine-N-oxide (0.098 mol) in 200 ml of methylene chloride was added dimethylcarbamyl chloride (0.1 mol) and the reaction mixture was allowed to react at room temperature under nitrogen for 24 hours. Additional dimethylcarbamyl chloride (0.1 mol) was added followed by cyanotrimethylsilane (0.22 mol), and the resulting mixture was allowed to react at 20° C. for 2 days. An additional 4 ml (0.03 mol) of cyanotrimethylsilane was then added, and the mixture was stirred at room temperature for another 24 hours. A solution of 200 ml of 10% K2CO3 was added to the reaction mixture and the resulting mixture was stirred for 45 minutes. The aqueous layer was extracted with 100 ml methylene chloride twice, the organic layers were combined and dried (K2CO3). After stripping the solvent, 16.9 g of crude product was isolated. The crude product obtained was chromatographed over Florisil® to isolate the desired products and the by-products with elution by the series of solvents: 2-acetyl-6-cyanopyridine (3a) (2g, 50% CH2Cl2 /hexane), 2-cyano-6-(1-cyano-1-trimethysilyloxy)ethylpyridine (3b) (0.81 g, CH2Cl2), 2-cyano-6-(1-cyano-1-dimethylcarbamoyloxy)ethylpyridine (3c) (1.67 g, 25:72 EtOAc/CH2Cl2), 2-(1-cyano-1-hydroxy)ethylpyridine (3d) (0.42 g, 50:50 EtOAc/CH2Cl2), and 2-(1-cyano-1-dimethylcarbamoyloxy)ethylpyridine-1-N-oxide (3e) (1.8 g, EtOAc). The products exhibited the following properties.

Workup

  1. customto react at room temperature under nitrogen for 24 hours
  2. customto react at 20° C. for 2 days
  3. stirringthe resulting mixture was stirred for 45 minutes
  4. extractionThe aqueous layer was extracted with 100 ml methylene chloride twice
  5. dry with materialdried (K2CO3)
  6. custom16.9 g of crude product was isolated
  7. customThe crude product obtained
  8. customwas chromatographed over Florisil®

Sources & evidence

ORD record
ord-3b52f7d520f64a7a93666b9731fdf243
Source dataset
uspto-grants-1996_07
Patent number
US05539117

Reaction notes

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